{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T13:24:17Z","timestamp":1763558657185,"version":"3.45.0"},"reference-count":60,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Very early pediatric-onset multiple sclerosis (POMS) is rare; clinical studies using disease-modifying treatments (DMTs) have not been performed. Clinicians rely on studies performed at older ages. This review resulted from difficulties faced by clinicians and the off-label use of DMTs at this age. Methods: A literature review of studies dated between 1982 and 2025 on very early POMS, specifically with onset before age 5, has been performed, searching for outcomes without or with DMTs. The curated database of the selected patients was analyzed using computed descriptive and integrated cohort-level estimates. The clinical, paraclinical, treatment, and outcome characteristics were analyzed. Statistical analysis used JASP, with GenAI-assisted verification. The treatment outcome of a 16-year-old patient with very early POMS starting at 2 years 4 months that consecutively received interferon, immunoglobulin, and Natalizumab is presented. Results: A total of 101 patients with very early POMS presented, at onset, with ataxic syndrome (57.4%), pyramidal syndrome (41.4%), ophthalmoplegia (10.3%), and optic neuritis (6.9%). In evolution, 22.7% had seizures. Half of the patients were not treated. Among those treated, acute steroid therapy was administered; 11 received the DMTs interferon, Glatiramer acetate, Dimethyl fumarate, and Azathioprine (three), with only two high-efficacy therapies (Natalizumab and Rituximab). Our patient had partial remission under interferon, relapses when stopped and replaced by immunoglobulin and 9 years relapse-free interval when Natalizumab was introduced. Conclusions: Early treatment with high-efficiency DMTs should be considered in very early POMS; association with known increased neuroplasticity at this age may improve prognosis, allowing good recovery of acquired disability.<\/jats:p>","DOI":"10.3390\/jcm14228133","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T12:55:31Z","timestamp":1763556931000},"page":"8133","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disease-Modifying Treatment Options in Very Early Onset Multiple Sclerosis\u2014What Choices Are There for Onset Under 5 Years of Age? A Systematic Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4156-6812","authenticated-orcid":false,"given":"Dana","family":"Craiu","sequence":"first","affiliation":[{"name":"Pediatric Neurology Discipline, Department of Neurosciences, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Pediatric Neurology Center of Expertise of Rare Pediatric Neurological Disorders, Alexandru Obregia Hospital, 041914 Bucharest, Romania"},{"name":"Romanian Group of Undiagnosed Rare Disorders of the Institute of Research and Development in Genomics, 020021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice Denisa","family":"Dica","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Discipline, Department of Neurosciences, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Pediatric Neurology Center of Expertise of Rare Pediatric Neurological Disorders, Alexandru Obregia Hospital, 041914 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Pomeran","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Discipline, Department of Neurosciences, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Pediatric Neurology Center of Expertise of Rare Pediatric Neurological Disorders, Alexandru Obregia Hospital, 041914 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Pescaru","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Discipline, Department of Neurosciences, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Pediatric Neurology Center of Expertise of Rare Pediatric Neurological Disorders, Alexandru Obregia Hospital, 041914 Bucharest, Romania"},{"name":"Romanian Group of Undiagnosed Rare Disorders of the Institute of Research and Development in Genomics, 020021 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shay","family":"Menascu","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Demyelinating Pediatric Service, Multiple Sclerosis Center, Sheba Medical Ceter, Tel Aviv 6997801, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-1282","authenticated-orcid":false,"given":"Mihaela","family":"Simu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Medicine and Pharmacy \u201cVictor Babes\u201d, 300041 Timisoara, Romania"},{"name":"Second Neurology Clinic of \u201cPius Br\u00eenzeu\u201d Emergency Clinical County, Hospital, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ejpn.2025.01.006","article-title":"Characterization of children with early onset pediatric multiple sclerosis","volume":"54","author":"Kauth","year":"2025","journal-title":"Eur. 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